Taxane Synthesis through Intramolecular Pinacol Coupling at C-1−C-2. Highly Oxygenated C-Aromatic Taxanes

Abstract

Chiral, nonracemic intramolecular pinacol coupling substrates 3/20 and 30 have been prepared from ethyl isopropyl ketone and acryloyl chloride, which provide the A-ring and either o-iodobenzyl alcohol or 2,4-dimethoxybenzyl alcohol, which provide the respective aromatic C-rings, in 14−16 linear steps in overall yields of approximately 20%. Potential pinacol coupling substrate 23 could not be made available for investigation due to intervening pinacol rearrangement in the acetonide formation step. 3/20 undergo stereoselective cyclizations mediated by TiCl4−Zn in which the C-9 oxygen substituent plays the dominant role in determining the stereochemical outcome at C-1 and C-2 in the respective tricyclic products 4 and 21. The formation of 21 is the more stereoselective process. The reagent of choice for the transformation of 30 into 31 is SmI2, which, although less stereoselective than TiCl4−Zn, leads to higher yielding carbon−carbon bond formation relative to carbonyl reduction. These pinacol cyclizations are interpreted to occur through endo boat-chair transition structures that prefer to orient the developing C-2 substituent and the preexisting C-9 substituent equatorially. Pinacol product 31 was converted through three additional steps into 40 having a B-ring closely related to that of taxol. We believe that these studies indicate pinacol cyclizations at C-1−C-2 to have considerable potential for producing advanced intermediates for syntheses of taxol and related complex taxanes.

Twenty five years of organic chemistry with diiodosamarium

“…products such as carbohydrates and in the total syntheses. For example, several taxoides and taxol syntheses took advantage of SmI 2 chemistry in a cyclization step or in the reductive removal of a functional group [44][45][46]. Asymmetric synthesis also benefited of samarium diiodide.…”

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

“…By following the known procedures, monoiodination of the commercially available methyl 3,5-dimethoxybenzoate, 3,5-dimethoxybenzaldehyde, and 3,5-dimethoxybenzyl alcohol under the influence of either I 2 /silver trifluoroacetate or N -iodosuccinimide afforded 1 [32–34], 2 [35], and 7 [36–37], respectively (Scheme 2). The hydroxy group of 7 was protected as an acetate, providing 3 in 96% yield.…”

Taxol: Synthesis, Bioactive Conformations, and Structure-Activity Relationships in Its Analogs

“…Intramolecular cyclization of the latter afforded diol 31 containing completed ring A. Modification of functional groups in the tricyclic system and building up ring D (as in the Wender synthesis) resulted in formation of compound 22 [16,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] which was brought into reaction with O-benzyl-N-benzoylphenylisoserine (32) in the presence of bis(2-pyridyl) thiocarbonate to 19 320 obtain 2'-benzyl-7-triethylsilyltaxol (33). Derivative 33 was converted into taxol (1) in two steps [16].…”